Concentration-flux relations for a multicellular biological membrane with metabolism

A mathematical model is described for the simultaneous diffusion and metabolism of a chemical penetrating a multicellular biological membrane such as skin. Metabolism is assumed to follow saturable Michaelis-Menten kinetics, which leads to nonlinear relationships between the applied concentration an...

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Bibliographic Details
Published in:Mathematical biosciences 1993-05, Vol.115 (1), p.103-117
Main Author: Auton, Timothy Robert
Format: Article
Language:English
Subjects:
560300 - Chemicals Metabolism & Toxicology
ALGORITHMS
ANIMAL TISSUES
BIOCHEMICAL REACTION KINETICS
Biological and medical sciences
BODY
CALCULATION METHODS
CELL CONSTITUENTS
CELL MEMBRANES
dermal penetration
DIFFUSION
ENZYMES
EPIDERMIS
EPITHELIUM
General pharmacology
HAZARDOUS MATERIALS
Humans
In Vitro Techniques
Isoflurophate - metabolism
Isoflurophate - pharmacokinetics
KINETICS
MATERIALS
MATHEMATICAL LOGIC
MATHEMATICAL MODELS
Mathematics
Medical sciences
MEMBRANES
Membranes - metabolism
METABOLISM
Models, Biological
MOLECULES
NONLINEAR PROBLEMS
ORGANIC COMPOUNDS
ORGANS
PERMEABILITY
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
PROTEINS
RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT
REACTION KINETICS
SKIN
Skin - metabolism
TISSUES
TOXIC MATERIALS
toxicology
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Summary:A mathematical model is described for the simultaneous diffusion and metabolism of a chemical penetrating a multicellular biological membrane such as skin. Metabolism is assumed to follow saturable Michaelis-Menten kinetics, which leads to nonlinear relationships between the applied concentration and the metabolic and diffusive fluxes through the membrane. Approximate concentration-flux relations are derived under limiting conditions, and a computational method is described for the general case. The major barrier to dermal penetration of very lipophilic molecules is thought to be the viable tissues (viable epidermis and some of the dermis) underlying the stratum corneum, and some molecules are known to be metabolized by enzymes within these tissues. It is proposed to use the model to describe penetration and metabolism of such lipophilic molecules within the viable tissues of the skin.
ISSN:0025-5564
1879-3134
DOI:10.1016/0025-5564(93)90048-F